Entamoeba histolytica

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Entamoeba histolytica

• cosmopolitan distribution
• no animal reservoirs
• facultative pathogen
• most clear the infection spontaneous in 6-12
  months with mild or no symptoms
• can cause a serious invasive disease
• worldwide incidence 0.2-50
• estimated that 10 of worlds population may be
  infected
• 50 million cases invasive amebiasis/yr
• 100,000 deaths/yr

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Facultative Pathogenicity of Entamoeba histolytica

• 1875 Lösch correlated dysentery with amebic
  trophozoites
• 1925 Brumpt proposed two species E. dysenteriae
  and E. dispar
• 1970's biochemical differences noted between
  invasive and non-invasive isolates
• 80's/90's several antigenic and DNA differences
  demonstrated
• rRNA 2.2 sequence difference
• 1993 Diamond and Clark proposed a new species
  (E. dispar) to describe non-invasive strains
• 1997 WHO accepted two species

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Entamoeba histolytica Life Cycle
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Excystation

• cyst wall disruption
• ameba emerges
• nuclear division (4?8)
• cytoplasmic division (8 amebala)
• trophozoites colonize large intestine
• feed on bacteria and debris
• replicate by binary fission

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Excystation

• cyst wall disruption
• ameba emerges
• nuclear division (4?8)
• cytoplasmic division (8 amebala)
• trophozoites colonize large intestine
• feed on bacteria and debris
• replicate by binary fission

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Encystation

• trophozoite rounds up
• secretion of cyst wall
• aggregation of ribosomes ( chromatoid bodies)
• 2 rounds of nuclear division (1?4 nuclei)
• survive weeks to months

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immature cyst
mature cyst
trophozoite
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Pathogenesis of Amebiasis

• NON-INVASIVE
• ameba colony on intestinal mucosa
• asymptomatic cyst passer
• non-dysenteric diarrhea, abdominal cramps, other
  GI symptoms
• INVASIVE
• necrosis of mucosa ? ulcers, dysentery
• ulcer enlargement ? dysentery, peritonitis
• metastasis ? extraintestinal amebiasis

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• ulcers with raised borders
• little inflammation between lesions

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• flasked-shaped ulcer
• trophozoites at boundary of necrotic and healthy
  tissue
• trophozoites ingesting host cells
• dysentery (blood and mucus in feces)

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hematophagous trophozoites
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Lateral and Downward Expansion of Ameba into
Lamina Propria
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Disease Manifestations

• ulcer enlargement ? severe dysentery
• perforation of intestinal wall ? peritonitis
• local abscesses
• 2o bacterial infections
• occasional ameboma (amebic granuloma)
• cessation of cyst production

ameboma inflammatory thickening of intestinal
wall around the abscess (can be confused with
tumor)
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• Extraintestinal Amebiasis
• metastasis via blood stream
• primarily liver (portal vein)
• other sites less frequent
• ameba-free stools common
• high antibody titers

• Amebic Liver Abscess
• chocolate-colored pus
• necrotic material
• usually bacteria free
• lesions expand and coalesce
• further metastasis, direct extension or fistula

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• Pulmonary Amebiasis
• rarely primary
• rupture of liver abscess through diaphragm
• 2o bacterial infections common
• fever, cough, dyspnea, pain, vomica

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• Cutaneous Amebiasis
• intestinal or hepatic fistula
• mucosa bathed in fluids containing trophozoites
• perianal ulcers
• urogenital (eg, labia, vagina, penis)

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• Cutaneous Amebiasis
• intestinal or hepatic fistula
• mucosa bathed in fluids containing trophozoites
• perianal ulcers
• urogenital (eg, labia, vagina, penis)

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• Cutaneous Amebiasis
• intestinal or hepatic fistula
• mucosa bathed in fluids containing trophozoites
• perianal ulcers
• urogenital (eg, labia, vagina, penis)

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Facultative Pathogenicity

• 85-90 of infected individuals are asymptomatic
• 10 of the symptomatic will develop severe
  invasive disease

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Molecular Epidemiology

• molecular probes used to survey for E. dispar
  and E. histolytica
• E. dispar 10-fold gt E. histolytica
• discrete endemic pockets of E. histolytica
• many asymptomatic E.h. infections
• 10 of the E.h. infections are associated with
  invasive amebiasis
• 25 seropositive for E. histolytica in endemic
  areas

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pathogenecity ability to cause disease (genetic component)
virulence relative capacity to cause disease (degree of pathology)

• a pathogen has an inherent ability to break host
  cell barriers
• virulence usually correlates with ability to
  replicate within host
• various degrees of virulence may be exhibited
  depending on conditions

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• contact-dependent killing of epithelial cells
• breakdown of tissues (extracellular matrix)
• secreted proteases?
• contact-dependent killing of neutrophils,
  leukocytes, etc.

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Galactose Inhibitable Adherence Protein

• trophozoites adhere to mucins, epithelial cells,
  leukocytes, etc
• mediated by galactose-inhibitable lectin activity
• lectin activity due to surface protein (GIAP)
• 170 kDa heavy chain mediates binding (multigene
  family)
• 35 kDa light chain anchor to membrane
• a-GIAP Abs abrogate complement resistance
• 85 identity between Eh and Ed
• Are there differences in adherence?
• after contact the target cell is lysed and
  phagocytosed by the trophozoite

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Host Cell Lysis and Phagocytosis

• Amebapore
• pore-forming peptide
• potent anti-bacterial activity
• located in vacuoles, not secreted
• Eh and Ed sequences are 95 identical
• Glu?Pro change breaks a-helix
• Ed had 80 less activity than Eh

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Entamoeba Proteases

• Eh expresses and secretes higher levels of
  cysteine proteases
• 6 cys-protease genes (ehcp1-6)
• ehcp1 and 5 are missing in Ed
• 90 inhibition of ehcp5 did not affect
  trophozoite mediated destruction of host cell
  monolayers

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• Intestinal Symptoms
• range
• mild to intense
• transient to long lasting
• nondysenteric
• diarrhea
• cramps
• flatulence
• nausea
• dysenteric
• blood/mucus in stools
• cramps/pain
• tenesmus
• ameboma
• palpable mass
• obstruction

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Antigen Detection Assay
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Control and Epidemiology
Treatment

• asymptomatic
• iodoquinol or paromomycin
• endemic areas?
• symptomatic
• metronidazole or tinidazole
• followed by lumenal agents
• drain liver abscess
• only with high probability of rupture!

• avoid fecal-oral transmission
• not normally associated with travelers diarrhea
• gt 1 month stay
• institutions
• mass drug treatment little affect
• ? staff and improved housing conditions lowers
  prevalence
• male homosexuals
• 40-50 in NYC and SF during late 70s
• lower since AIDS/safe sex